Parkinson's Disease (PD) is a neurodegenerative disease caused by progressive accumulation of abnormal intracellular aggregates of alpha synuclein (α-Syn) protein existing as Lewy bodies, the pathological hallmark of the disease. Lewy bodies first appear in the olfactory bulb and medulla and gradually spread to midbrain, at which time, the first motor signs of PD appear (Braak et al., 2002). Concomitantly, inflammatory responses from resident microglia result in T-cell recruitment, setting off an exacerbating inflammatory cascade (Brochard et al., 2009). Together, these events lead to the progressive demise of nigrostriatal dopaminergic neurons, resulting in the classical clinical signs of bradykinesia, rest tremor, and rigidity. Symptomatic relief is provided by dopamine replacement, but the underlying disease process continues unabated. The advances in research with immunotherapies for AD have opened new opportunities for treatment of PD. Vaccines developed against α-Syn protein and administration of antibodies against α-Syn have been studied by several research groups (Hirsch et al., 1985, Masliah et al., 2005, Mougenot et al., 2010).
Dendritic cells (DCs) play a central role in initiating the primary immune response, through antigen presentation to T cells (Steinman, 1991, Banchereau and Steinman, 1998). Moreover, recent studies have revealed that DCs can induce proliferation of B cells and directly stimulate production of antibodies (Dubois et al., 1997, Dubois et al., 1999). DCs also govern immunoglobulin class-switching, such as immunoglobulin A2 expression (Fayette et al., 1997) indicating that DCs regulate the humoral immune response as well, in part via a direct interaction with B cells (Clark, 1997).
Many immunotherapies have been developed since the first vaccine against Alzheimer's disease (AD) was published. Clinical trials have also been conducted by several companies, but there is no success yet. The vaccines and immunotherapies against neurodegenerative diseases have to be able to deal with the pathological protein as well as the impaired immune system, because age is the most important risk factor for such disease, and the immune system declines with aging.
Antigen-sensitized DCs have been used as vaccines in many fields (Gajewski et al., 2001, Satthaporn and Eremin, 2001, Barrou et al., 2004, Cohen et al., 2005, Loveland et al., 2006, Mittendorf et al., 2006). DC vaccines also have already been approved by the FDA for clinical use in various diseases, such as HIV and cancer (Ide et al., 2006, Pellegatta et al., 2006). DCs sensitized with mutant Aβ peptides were used to vaccinate a mouse model of AD, without eliciting a generalized inflammatory response (Cao et al., 2008).